Virtually all skeletal growth is the result of the orderly division and maturation of the cells of the epiphyseal growth plate. Normal skeletal development is dependent on the proper control of this process. This proposal is based on the applicants' previous observations that peptide growth factors participate in this control. The goal of the proposed studies is to elucidate the mechanisms by which selected growth factors regulate growth plate chondrocytes. The investigators hypothesize that growth factor interaction plays an important role in the regulation of growth plate chondrocytes. One aim of these studies is to test this hypothesis by examining the individual and interactive effects of selected growth factors with respect to mitotic and differentiated chondrocyte functions in vitro. Cell culture, metabolic labelling, radioimmunoassay, immunoinhibition, Northern and in situ hybridization methods will be used to identify interactions and begin to elucidate their mechanisms. The second aim is to test the postulate that the effects of the calciotropic hormones, calcitonin and PTH, on growth plate chondrocytes are modulated by peptide growth factors. Specifically, regulation of chondrocyte PTH receptor and calcitonin receptor expression by selected growth factors will be examined by cell biological and molecular biological techniques. The third aim is to assess the ability of exogenously administered growth factors to regulate skeletal growth in vivo.Using a rat model, the action and interaction of selected factors will be evaluated by metabolic and in situ hybridization techniques. The long-term objective of these studies is to help achieve a basic understanding of the mechanisms regulating skeletal growth. Only with such information can abnormalities of skeletal growth and repair be understood and the potential contribution of growth factors to clinical problems eventually be determined.